Biomedical subjects
Publications and source records attributed to James R Johnson.
Among 1,102 recent Escherichia coli clinical isolates, clonal group A was identified in 17 of 20 (U.S. and non-U.S.) geographic locales, mainly among U.S. isolates (9% vs. 3%; p < 0.001) and those resistant to trimethoprim-sulfamethoxazole (10% vs. 1.7%; p < 0.001). The extensive antimicrobial resistance and virulence profiles of clonal group A may underlie its recent widespread emergence.
In a recent, population-based survey of 3,996 persons in Indonesia, fluoroquinolone (FQ)-resistant Escherichia coli was prevalent in the fecal flora of 6% of patients at hospital admission and 23% of patients at discharge, but not among healthy relatives or patients visiting primary healthcare centers (2%). Molecular typing showed extensive genetic diversity with only limited clonality among isolates. This finding suggests that independent selection of resistant mutants occurs frequently. FQ-resistant isolates exhibited a higher rate of spontaneous mutation, but sparser virulence profiles, than FQ-susceptible isolates from the same population. The resistant isolates belonged predominantly to phylogenetic groups A (57%) and B1 (22%) but also to the moderately virulent group D (20%). Hypervirulent strains from the B2 cluster were underrepresented (1%). Because FQ-resistant E. coli can cause disease, especially nosocomial infections in immunocompromised patients, spread of such strains must be stopped.
Stool carriage of drug-resistant Escherichia coli in home-living residents of a rural community was examined. Carriage of nalidixic acid-resistant E. coli was associated with recent use of antimicrobial agents in the household. Household clustering of drug-resistant E. coli was observed. Most carriers of drug-resistant E. coli lacked conventional risk factors.
BACKGROUND: The multistate occurrence of cases of urinary tract infection (UTI) caused by trimethoprim-sulfamethoxazole (TMP-SMZ)-resistant Escherichia coli strains belonging to a single clonal group (designated as clonal group A [CgA]) in the United States has raised an intriguing hypothesis that these infections may have been spread by contaminated food products. The present study attempted to determine if CgA strains could be traced to food animals. METHODS: A total of 495 animal and environmental E. coli isolates, which belonged to serogroups O11, O17, O73, and O77 and were collected between 1965 and 2002 by the Gastroenteric Disease Center at Pennsylvania State University (University Park, PA), were further subtyped by antimicrobial drug susceptibility, enterobacterial repetitive intergenic consensus (ERIC2) PCR, random amplified polymorphic DNA analysis, pulsed-field gel electrophoresis (PFGE), and virulence profile pattern. RESULTS: Of 495 isolates, 128 (26%) had an ERIC2 PCR electrophoretic pattern indistinguishable from that of the human prototype CgA strain, and 14 CgA isolates were resistant to TMP-SMZ. Cluster analysis of PFGE patterns showed that 1 of these 14 isolates, obtained from a cow in 1988, was 94% similar to a CgA uropathogenic human-associated E. coli strain. The pattern for this isolate was included among a cluster of PFGE patterns for 5 human-associated UTI isolates that were >80% similar to each other. CONCLUSIONS: These observations suggest that drug-resistant, uropathogenic human-associated E. coli strains potentially have an animal origin. The possibility that human drug-resistant UTI could be a foodborne illness has serious public health implications.
Molecular analysis of 63 Escherichia coli urine isolates showed that pyelonephritis (n=23) and prostatitis (n=17) isolates exhibited more virulence factors (VFs) among the 35 sought than did cystitis isolates (n=23). Several nontraditional VFs--including bmaE (M fimbriae), gafD (G fimbriae), fyuA (yersiniabactin receptor), ireA and iroN (novel siderophore receptors), cvaC (colicin [microcin] V), traT (serum-resistance associated), ibeA (invasion of brain endothelium), ompT (outer membrane protease T), and malX (pathogenicity island marker)--either differentiated significantly between syndromes (despite small numbers of isolates and possible multiple-comparison artifacts) or were broadly prevalent. Thus, interventions that target conserved uro-VFs may be possible, despite the likely existence of syndrome-specific pathogenetic mechanisms and/or host defense systems.
BACKGROUND: Escherichia coli is the most common cause of gram-negative bloodstream infections, causing an estimated 40,000 deaths from sepsis each year in the United States. The present study sought to determine specifically which virulence factors (VFs) and phylogenetic groups of E. coli are epidemiologically associated with bacteremia. METHODS: E. coli isolates from 63 veterans with bacteremia and rectal isolates from 71 matched uninfected control subjects were compared both for phylogenetic group and for the presence of VFs and O antigens. RESULTS: Bacteremia isolates exhibited a significantly greater prevalence of most VFs studied. In multivariate logistic regression analysis, ompT (outer membrane protein T) was the strongest VF predictor of bacteremia (P<.001). Despite the concentration of most individual VFs within group B2, bacteremia and rectal isolates differed little by phylogenetic distribution, a finding explained by the greater prevalence of VFs among bacteremia isolates than rectal isolates within groups B2 and D. CONCLUSIONS: Although phylogenetic group partially corresponds with virulence potential in E. coli bacteremia, VFs are more-powerful predictors of pathogenic potential. Bacteremia isolates exhibit an arsenal of VFs that distinguishes them from rectal isolates from uninfected hosts, which makes these differences attractive potential targets in vaccine or drug development.
BACKGROUND: Increases in antimicrobial resistance in Escherichia coli have been paralleled by an increasing incidence of E. coli sepsis, suggesting a possible link between resistance and virulence. METHODS: All 76 multidrug-resistant (MDR) E. coli isolates (i.e., those resistant to > or =3 antimicrobial agents, including ampicillin, ceftazidime, trimethoprim-sulfamethoxazole, gentamicin, and ciprofloxacin) reported to the Tracking Resistance in the United States Today studies during 2000-2001 and 76 closely matched pansusceptible control isolates were studied. Extended virulence profiles and E. coli phylogenetic group (A, B1, B2, or D) were compared between groups. RESULTS: The MDR isolates, which represented predominantly non-B2 phylogenetic groups (91%), exhibited significantly reduced molecular virulence, compared with the predominantly group B2-derived control isolates (58%). Only 30% of MDR isolates, compared with 61% of control isolates (P<.001), qualified as extraintestinal pathogenic E. coli (ExPEC), and even these isolates exhibited significantly lower virulence scores than did susceptible ExPEC (7.25 vs. 9.0; P=.001). Phylogenetic differences accounted for the apparent virulence differences between MDR and control isolates. CONCLUSIONS: These findings argue against a direct link between virulence traits and antimicrobial resistance in E. coli. Instead, they call into question why non-B2 strains are more commonly MDR, with differential exposure to selection pressure (including in agriculture) as one possible explanation.
The susceptibility to 12 antimicrobial agents of 165 Escherichia coli isolates from women with acute uncomplicated pyelonephritis of mild to moderate severity was analyzed by geographic region in the US. Ampicillin, trimethoprim, and trimethoprim/sulfamethoxazole resistance exhibited a descending prevalence gradient from west to east. Composite antimicrobial resistance phenotypes also exhibited significant regional differences, with a greater prevalence of most combined resistance profiles seen in the Pacific region of the US, but with significant north-south variation for combined ampicillin/sulfisoxazole resistance. These findings suggest geographical segregation of resistant clones and/or resistance elements among uropathogenic E. coli within the US, which is relevant both to clinical practice and to understanding the basis for the current epidemic of antimicrobial resistance in E. coli.
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OBJECTIVE: To assess the prevalence and patterns of antimicrobial resistance among Escherichia coli strains isolated from the urine of women with cystitis or pyelonephritis and from fecal samples from dogs and healthy humans. DESIGN: Cross-sectional survey. SAMPLE POPULATION: Escherichia coli isolates from 82 women with cystitis, 170 women with pyelonephritis, 45 dogs, and 76 healthy human volunteers. PROCEDURE: Susceptibility to 12 antimicrobial agents was determined by means of disk diffusion testing as specified by the NCCLS. RESULTS: Overall, the 4 most common antimicrobial resistance patterns were resistance to ampicillin, sulfisoxazole, trimethoprim, and trimethoprim-sulfamethoxazole (n = 45 [12% of all isolates]); ampicillin alone (33 [9%]); ampicillin and sulfisoxazole (29 [8%]); and sulfisoxazole alone (14 [4%]). None of the isolates were resistant to ceftazidime, ciprofloxacin, nitrofurantoin, or piperacillin-tazobactam. Resistance was significantly more common and extensive among isolates from women with cystitis or pyelonephritis than among isolates from healthy humans or dogs. Resistance was least common among isolates from dogs. The only resistance phenotype that was more common among canine isolates than human isolates was resistance to sulfisoxazole alone. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that dogs are unlikely to be an important external reservoir of antimicrobial-resistant E. coli strains causing infections in humans. On the contrary the data suggest that dogs conceivably could acquire resistant E. coli strains from humans.
Antibiotics are an important class of therapeutic agents, which are used for the treatment of bacterial infectious diseases in a variety of animal species. Antibiotic therapy varies from treatment period to administration routes, depending on the animal species or the type of the disease being treated. Despite the fact that there are a wide variety of commercially available antibiotics, difficulties and problems associated with the administration of antibiotics to animals still exist. Thus, there is a great need and tremendous opportunity to develop long-acting antibiotic formulations for veterinary applications. In this review article, common approaches used to develop long-acting antibiotic formulations are summarized. The challenges and issues related to the development of these long-acting formulations are also discussed.
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Spread of biological species from primary into novel habitats leads to within-species adaptive niche differentiation and is commonly driven by acquisition of point mutations in individual genes that increase fitness in the alternative environment. However, finding footprints of adaptive niche differentiation in specific genes remains a challenge. Here we describe a novel method to analyze the footprint of pathogenicity-adaptive, or pathoadaptive, mutations in the Escherichia coli gene encoding FimH-the major, mannose-sensitive adhesin. Analysis of distribution of mutations across the nodes and branches of the FimH phylogenetic network shows (1) zonal separation of evolutionary primary structural variants of FimH and recently derived ones, (2) dramatic differences in the ratio of synonymous and nonsynonymous changes between nodes from different zones, (3) evidence for replacement hot-spots in the FimH protein, (4) differential zonal distribution of FimH variants from commensal and uropathogenic E. coli, and (5) pathoadaptive functional changes in FimH brought by the mutations. The selective footprint in fimH indicates that the pathoadaptive niche differentiation of E. coli is either in its initial stages or undergoing an evolutionary "source/sink" dynamic.
BACKGROUND: Dipyridamole and adenosine cause frequent side effects as a result of nonspecific adenosine receptor stimulation. Selective agonism of the adenosine A2A receptor should result in a similar degree of coronary vasodilation (and thus similar perfusion images) with fewer side effects. METHODS AND RESULTS: In a multicenter, randomized, single-blind, 2-arm crossover trial, 240 patients underwent 2 single photon emission computed tomographic (SPECT) imaging studies in random order, first after pharmacological stress with adenosine and a second study with the selective adenosine A2A receptor agonist binodenoson, using 1 of 4 dosing regimens. Safety, tolerability, and SPECT image concordance between the 2 agents were examined. Exact categorical agreement in the extent and severity of reversible perfusion defects ranged from 79% to 87%, with kappa values from 0.69 to 0.85, indicating very good to excellent agreement between binodenoson and adenosine. The risk of any safety event/side effect was significantly lower with any dose of binodenoson than with adenosine (P< or =0.01) because of a dose-related reduction in subjective side effects, as objective events were infrequent. There was a reduction in the severity of chest pain, dyspnea, and flushing in all binodenoson doses compared with adenosine (P<0.01), and the magnitude of severity reduction was dose-related. CONCLUSIONS: The selective adenosine A2A receptor agonist binodenoson results in an extent and severity of reversible perfusion defects on SPECT imaging similar to nonselective adenosine receptor stimulation, accompanied by a dose-related reduction in the incidence and severity of side effects.
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In a cross-sectional fecal prevalence survey involving 49 residents of a Veterans Affairs nursing home, 59% of subjects were colonized with extraintestinal pathogenic Escherichia coli (ExPEC), 22% were colonized with adhesin-positive E. coli, and 51% were colonized with fluoroquinolone-resistant E. coli. Among 80 unique isolates, adhesins correlated negatively and aerobactin correlated positively with fluoroquinolone resistance.
Isogenic Enterococcus faecalis strains that differ in their expression of aggregation substance (AS) and its cognate receptor, enterococcal binding substance (EBS), were compared for urovirulence in mice. Strain OG1SSp/pCF500 (inducible AS(+), constitutive EBS(+)) failed to outcompete isogenic derivative INY3000 (AS(-) EBS(-)) in the urine, bladders, or kidneys of mice harvested at 48 h postinoculation. Neither mouse nor human urine induced AS expression by OG1SSp/pCF500. Recombinant strain OG1SSp/pINY1801 (constitutive AS(+), EBS(+)) exhibited plasmid segregation that was as extensive in vivo as in vitro. These data suggest that AS and EBS do not contribute to upper or lower urinary tract colonization by E. faecalis and that growth in urine does not induce AS expression by strains carrying plasmids in the pCF10 family.